Cerebrotendinous xanthomatosis

Cerebrotendinous xanthomatosis
Other names	Cerebral cholesterosis
Cerebrotendinous xanthomatosis has an autosomal recessive pattern of inheritance.
Specialty	Medical genetics, endocrinology

Cerebrotendinous xanthomatosis (CTX), also called cerebral cholesterosis,^[1] is a rare inborn bile acid metabolism disorder caused by autosomal-recessive mutations in the CYP27A1 gene.^[2] CTX is characterized by a wide range of symptoms, including neurological and non-neurological issues.

The average age of symptom onset is 19 years, with central nervous system symptoms being the first indications. Neurological characteristics include Parkinsonism, epilepsy, dystonia, progressive ataxia, palatal myoclonus, intellectual disability, dementia, and psychiatric symptoms. CTX often results in cataracts during childhood. Adults with CTX often experience optic disk paleness and other ocular problems. Clinical symptoms include cardiovascular disease and premature atherosclerosis, with patients experiencing elevated levels of 27-hydroxycholesterol and decreased high-density lipoprotein cholesterol. CTX patients often experience osteoporosis and recurrent bone fractures, with gait abnormalities and little bone mass increasing the risk of falls. Chronic and intractable diarrhea is a common symptom, and gallstones, cholecystic polypus, and newborn cholestatic jaundice are also observed in some CTX patients. Xanthomas, typically developing in the second or third decade of life, can originate on various tendons.

The CYP27A1 gene, responsible for bile acid production, is mutated, reducing chenodeoxycholic acid and cholic acid, leading to increased synthesis of 7α-hydroxy-4-cholesten-3-one, precursor to cholestanol. This leads to cholesterol being converted into cholestanol and bile alcohol, causing tissue accumulation and various organ-related symptoms.

CTX diagnosis involves molecular genetic analysis, neuroimaging, biochemical testing, and clinical findings.

CTX management includes surgery, replacement therapy, and additional symptomatic treatment. Bile acids like taurocholic acid, ursodeoxycholic acid (UDCA), cholic acid, and chenodeoxycholic acid (CDCA) are often used. CDCA treatment is preferred for both neurological and non-neurological symptoms. Symptomatic treatment is crucial due to the wide range of symptoms associated with CTX.